Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymyxin B (0.01-1 mM), a polyamine antibiotic, inhibited both phorbol ester- and glucose-stimulated insulin secretion from isolated rat islets of Langerhans. This inhibition was rapidly reversible. Assay of the cytosolic protein kinase C by measurement of incorporation of labelled phosphate into a histone substrate demonstrated the presence of activity in islet extracts which could be stimulated by 12-O-tetradecanoylphorbol-13-acetate and inhibited by polymyxin B. These results suggest that protein kinase C plays a role in glucose-induced insulin secretion.
 ...
PMID:The effects of polymyxin B, a protein kinase C inhibitor, on insulin secretion from intact and permeabilized islets of Langerhans. 301 62

Activation of the Na+/H+ antiport mechanism was studied in human neutrophils by monitoring intracellular pH with a carboxyfluorescein derivative. N-formyl-methionyl-leucyl-phenylalanine (FMLP) and phospholipase C (PLC) induced biphasic pH changes. Amiloride, which inhibits the antiport, completely blocked alkalinization but enhanced acidification. Polymyxin B, which inhibits protein kinase C, only blocked alkalinization. Activation with phorbol 12-myristate 13-acetate (PMA) led to alkalinization only; this was inhibited by amiloride or polymyxin B. Thus, during polymorphonuclear leukocyte (PMN) activation, intracellular alkalinization appears to be mediated by an amiloride-sensitive Na+/H+ antiport. Antiport activity can also be blocked indirectly by inhibition of protein kinase C activity. Early intracellular acidification does not appear to require kinase activity but is observed when phospholipids are remodeled with PLC. The antiport was also activatable by hypertonic buffered media. This response did not appear to be mediated by protein kinase C because it was unaffected by polymyxin B. Finally, superoxide generation was investigated. It is affected by, but not soley controlled by, either antiport or protein kinase C activity.
 ...
PMID:Intracellular pH changes during neutrophil activation: Na+/H+ antiport. 302 17

The action of the cyclic peptide polymyxin B (a well known inhibitor of protein kinase C) on adrenal steroid synthesis was examined with Y-1 adrenal tumor cells. Polymyxin B produces a biphasic effect on the stimulation of steroid synthesis by 2 nM ACTH in these cells, with inhibition at low concentrations (less than 10 microM) and a return to control levels at high concentrations (greater than 100 microM). Polymyxin B does not inhibit the stimulatory effect of Bu2cAMP on steroidogenesis. Inhibition of the steroidogenic response to ACTH by a fixed concentration (20 microM) of polymyxin B is overcome by high concentrations of ACTH. Polymyxin B causes a concentration-dependent stimulation of steroid synthesis by Y-1 cells and, over the same concentration range, increases the production of cAMP by these cells. Polymyxin B also partially inhibits the increased production of the cyclic nucleotide produced by ACTH. In addition, polymyxin B inhibits binding of [125I](Phe2,Nle4)ACTH-(1-38) to Y-1 cells. Polymyxin B, like ACTH, promotes rounding of Y-1 cells and partially inhibits rounding produced by ACTH. These effects of polymyxin B are specific to the extent that polymyxins E1 and E2 do not exert similar effects. The actions of polymyxin B are not confined to transformed cells, since responses similar to those seen with Y-1 cells were also observed with cultured rat fasciculata cells. On the other hand, the effect of polymyxin B is specific for adrenal cells, since the cyclic peptide does not influence the steroidogenic response of rat Leydig cells to LH. It is concluded that polymyxin B is a partial agonist of ACTH which is likely to prove useful in studying the molecular basis of the interaction between ACTH and its adrenal receptor.
 ...
PMID:The effect of polymyxin B on steroidogenesis from adrenocortical cells. 303 70

The protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDB) enhanced in a concentration-dependent manner the electrically stimulated release of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) from rat amygdala slices in vitro. PDB enhanced the basal release of [3H]NA and [3H]DA as well. 4 alpha-Phorbol 12,13-didecanoate, which lacks the capacity to activate protein kinase C, was without effect on either basal or electrically stimulated release of [3H]NA and [3H]DA. Polymyxin B, which is a relatively selective protein kinase C inhibitor, decreased in a concentration-dependent manner the electrically stimulated release of both [3H]NA and [3H]DA from amygdala slices, whereas it enhanced the basal release of both neuromessengers. In the presence of 1.5 X 10(-7) M PDB, a concentration which when added to the superfusion medium alone doubled the electrically stimulated release of both [3H]NA and [3H]DA, polymyxin B again decreased in a concentration-dependent manner the release of both neuromessengers. At all polymyxin B concentrations used, the effect of the PKC inhibitor, expressed as percent inhibition, in the presence of PDB was approximately the same as that observed in the absence of PDB. This suggests that the antagonism between PDB and polymyxin B at the level of protein kinase C is not a competitive one. The effects of PDB and polymyxin B on basal release were additive. Taken together, these data suggest that in the amygdala presynaptically localized protein kinase C plays a role in signal transduction processes related to the exocytotic secretion of NA and DA from their nerve terminals.
 ...
PMID:Basal and electrically stimulated release of [3H]noradrenaline and [3H]dopamine from rat amygdala slices in vitro: effects of 4 beta-phorbol 12,13-dibutyrate, 4 alpha-phorbol 12,13-didecanoate and polymyxin B. 304 Jan 79

Cardiac sarcolemma was purified from canine ventricles. Enrichment of the sarcolemmal membranes was demonstrated by the high (Na+ + K+)-ATPase activity of 28.0 +/- 1.5 mumol Pi/mg protein per h and the high concentration of muscarinic receptors with the Bmax of 8.2 +/- 2.5 pmol/mg protein as determined by [3H]QNB binding. The purified sarcolemma also contains significant levels of a membrane-bound Ca2+ and phospholipid-dependent protein kinase (protein kinase C). To elucidate the protein kinase C activity in sarcolemma, a prior incubation of the membranes with EGTA and Triton X-100 was necessary. The specific activity of protein kinase C was found to be 131.4 pmol Pi/mg per min, in the presence of 6.25 micrograms phosphatidylserine and 0.5 mM CaCl2. Treatment of sarcolemma with 12-O-tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13-dibutyrate (PBu2) resulted in a concentration-dependent activation of protein kinase C activity. The effect of TPA and PBu2 on protein kinase C in sarcolemma was independent of exogenous Ca2+ and phosphatidylserine. Polymyxin B inhibited phorbol-ester-induced activation of protein kinase C activity. The distribution of protein kinase C in the cytosolic fraction was also examined. The specific activity of the kinase in the cytosolic fraction was 59.7 pmol Pi/mg per min. However, the total protein kinase C activity in the cytosol was 213500 pmol Pi/min, compared to that of 1025 pmol Pi/min in the sarcolemma isolated from approx. 100 g of canine ventricular muscle. Several endogenous proteins in cardiac sarcolemma were phosphorylated in the presence of Ca2+ and phosphatidylserine. The major substrates for protein kinase C were proteins of Mr 94 000, 87 000, 78 000, 51 000, 46 000, 11 500 and 10 000. Most of these substrate proteins have not been identified before. Other proteins of Mr 38 000, 31 000 and 15 000 were markedly phosphorylated in the presence of Ca2+ only. Phosphorylation of phospholamban (Mr 27 000 and 11 000) was also stimulated in the presence of Ca2+ and phosphatidylserine, but the low Mr form of phospholamban was distinct from two other low Mr substrate proteins for protein kinase C. Polymyxin B was more selective in inhibiting the protein kinase C dependent phosphorylation. On the other hand, trifluoperazine selectively inhibited the phosphorylation of phospholamban and Mr 15 000 protein. Although the exact function of this kinase is unknown, based on these observations, we believe that protein kinase C in the cardiac sarcolemma may play an important role in the cell-surface-signal regulated cardiac function.
 ...
PMID:Characterization of the membrane-bound protein kinase C and its substrate proteins in canine cardiac sarcolemma. 308 70

1. The release of radioactivity from rat isolated atria preloaded with [3H]-noradrenaline ([3H]-NA) evoked by electrical field stimulation (2 Hz, 1 ms, 60 s) of intraneuronal sympathetic nerves, high potassium (64.7 mM) or tyramine (0.3 micron) was used as an index of noradrenaline release. 2. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) produced a concentration-dependent enhancement of field stimulation-induced outflow of radioactivity, whereas polymyxin B, an inhibitor of protein kinase C, reduced [3H]-NA release evoked by field stimulation. The enhancement observed in the presence of PMA was attenuated by polymyxin B (10 and 70 microns). 3. Release of noradrenaline evoked by membrane depolarization in a high potassium medium was similarly affected by PMA and polymyxin B. 4. In contrast, the release of noradrenaline evoked by the indirectly acting sympathomimetic amine, tyramine, was not altered by PMA. Polymyxin B in a concentration of 70 microns, but not 10 microns caused a slight reduction in tyramine-induced outflow of radioactivity. 5. The spontaneous outflow of radioactive compounds was not affected by either PMA or polymyxin B in the bathing medium. 6. The findings suggest that protein kinase C may play a role in the exocytotic release of noradrenaline but not in the displacement of noradrenaline by indirectly acting sympathomimetic amines.
 ...
PMID:The influence of activation or inhibition of protein kinase C on the release of radioactivity from rat isolated atria labelled with [3H]-noradrenaline. 317 9

Contractions of the dorsal pedal artery and saphenous vein to phorbol 12,13-dibutyrate (PDBu), 12-O-tetradecanoylphorbol 13-acetate (TPA), and 4 alpha-phorbol 12,13-didecanoate (4 alpha-phorbol) were measured from dogs with and without pacing-induced heart failure. The effects of polymyxin B (a relatively selective protein kinase C inhibitor), nifedipine (calcium channel blocker), and prazosin (alpha 1-adrenoceptor antagonist) were examined on the contractions developed to PDBu before heart failure, after 1 week of pacing, and at end-stage heart failure. PDBu and TPA, but not 4 alpha-phorbol, produced concentration-dependent increases in contractile force in both the artery and the vein. In the dorsal pedal artery, efficacy of and sensitivity to PDBu and TPA were enhanced after 1 week of pacing, but returned to control level at end-stage heart failure. In the saphenous vein, the concentration-effect curve to PDBu was displaced to the left after 1 week of pacing; EC50 values for PDBu were 3.2 x 10(-9) and 3.2 x 10(-8) M for 1 week paced and control, respectively. Polymyxin B significantly decreased the efficacy of PDBu in the dorsal pedal artery at all time points, but was less effective with advancing heart failure. In contrast, in the vein, there was a significant increase in inhibitory potential at end-stage heart failure. In all cases, nifedipine inhibited PDBu in a concentration-dependent manner. With the progression of heart failure, the contractions of the saphenous vein, developed to PDBu, became more sensitive to inhibition by nifedipine. Prazosin failed to inhibit vascular effects of PDBu. These results are discussed in terms of protein kinase C involvement in vascular contractions and its role in the pathogenesis of heart failure.
 ...
PMID:Peripheral vascular smooth muscle responsiveness to tumour-promoting phorbol esters in pacing-induced heart failure. 758 33

We have proposed that ischemic preconditioning in the rabbit heart is initiated by adenosine A1 receptor stimulation which results in an upregulation of protein kinase C (PKC). Subsequent sustained ischemia then causes renewed stimulation of adenosine A1 receptors with rapid reactivation of PKC and phosphorylation of a target protein(s) which mediates the protection. If the above theory is correct then angiotensin II (AII) receptor stimulation, which is known to activate PKC, should also protect the heart. Isolated rabbit hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Infarct size was determined by tetrazolium staining. Pretreating hearts with 100 mM AII for 5 min, followed by 10 min of drug-free perfusion prior to the prolonged ischemia limited infarction (7.2 +/- 2.0% of the risk area v 31.1 +/- 3.4% in control animals, P < 0.01). This protection could be blocked by the AT1 receptor blocker losartan (10 microM), but not by the AT2 receptor blocker PD 123319 (10 microM). Polymyxin B (50 microM), a PKC inhibitor, also blocked the protective effect of AII. These observations demonstrated that activation of PKC by AT1 receptor stimulation prior to ischemia does mimic ischemic preconditioning. Following AII infusion, administration, during the 30 min ischemic period, of either SPT [8-(p-sulfophenyl)theophylline] (an adenosine receptor blocker) or losartan failed to block AII's protective effect. However, co-administration of SPT and losartan did abort AII's protection suggesting that AII may not be completely washed out during the 10 min drug-free perfusion allowing residual agonist to reactivate PKC during the 30 min ischemia even when adenosine receptors are blocked. Thus, if only one of the receptors (AT1 or adenosine) were activated during the ischemic period, protection would occur. We conclude that activation of PKC by AII, prior to ischemia, can limit myocardial infarction. While PKC must be reactivated during ischemia to realize protection, the specific receptor type initiating reactivation is not crucial.
 ...
PMID:Pretreatment with angiotensin II activates protein kinase C and limits myocardial infarction in isolated rabbit hearts. 760 6

K+ conductance species in a human intestinal epithelial cell line (Intestine 407) were studied in connection with their sensitivities to an intestinal secretagogue, histamine, using the tight-seal whole-cell patch-clamp technique. Applications of positive command pulses rapidly induced outward K+ currents. The conductance became progressively larger with increasing command voltages, exhibiting an outwardly rectifying current voltage relation. Inward K+ currents were also rapidly activated upon applications of hyperpolarizing pulses at potentials negative to the equilibrium potential of K+ (EK), and the conductance inwardly rectified. Application of a Ca2+ ionophore, ionomycin, brought about activation of additional K+ currents. An inhibitor of protein kinase C, polymyxin B, did not affect the ionomycin-induced response. Histamine (10-200 microM) also activated a similar K+ current which was abolished by cytosolic Ca2+ chelation. Under conditions where Ca2+ mobilization was minimized, histamine was found to significantly augment inwardly rectifying K+, but suppress outwardly rectifying K+, currents. Polymyxin B blocked these effects of histamine. An activator of protein kinase C, 1-oleoyl-2-acetylglycerol, mimicked the histamine effects. It is concluded that the intestinal epithelial cell has three distinct types of K+ conductance and that histamine modulates not only Ca(2+)-activated K+ conductance via Ca2+ mobilization, but also inward- and outward-rectifier K+ conductances via activation of protein kinase C.
 ...
PMID:Histamine modulates three types of K+ current in a human intestinal epithelial cell line. 783 68

Ischemic preconditioning in the rabbit is initiated by adenosine A1-receptor stimulation, which activates protein kinase C (PKC). Additionally, alpha 1-adrenergic agonists can similarly protect ischemic myocardium, but there has been confusion about the role adenosine receptors play in this protection. To characterize the interaction between adrenergic and adenosine receptors and to study the possible role of PKC in this protection, we used isolated rabbit hearts perfused with oxygenated Krebs' buffer. All hearts were subjected to 30 minutes of regional myocardial ischemia and 2 hours of reperfusion. Infarct size was determined by triphenyltetrazolium staining. Pharmacologic preconditioning in hearts with a 5-minute phenylephrine (PE) infusion 10 minutes before the prolonged regional ischemia resulted in significantly smaller infarcts (9.7 +/- 1.3% of risk area) than in control hearts (31.0 +/- 2.6%, P < .05). This protection could be effectively blocked by administration of the alpha-adrenergic blocker phenoxybenzamine. Methoxamine, an alpha 1a-selective agonist, failed to protect, whereas the alpha 1b-selective antagonist chloroethylclonidine aborted the protective effect of PE. Polymyxin B, an inhibitor of PKC, also blocked the protective effect of PE, implying that PKC has an important role in preconditioning. The adenosine receptor blocker 8-(p-sulfophenyl)theophylline (SPT) given at the same time as the PE infusion did not affect the protection, implying that an alpha 1-agonist could initiate protection independent of adenosine, presumably by direct coupling to PKC. However, the protective effect of PE could be blocked if SPT were administered during the 30-minute regional ischemia. This observation suggested that adenosine receptor occupancy is necessary during long ischemia to reactivate PKC and mediate the protection. However, the addition of a second PE infusion beginning 5 minutes before and continuing throughout the long ischemic period restored the protective effect of PE despite the presence of SPT. Thus, as long as at least one of the receptors (alpha 1-adrenegic or adenosine A1) is activated during long ischemia, protection will be realized. These data indicate that alpha 1 receptors do not precondition through an adenosine intermediate but that alpha 1-adrenergic and adenosine receptors activate parallel pathways within the myocyte that can trigger and mediate protection.
 ...
PMID:alpha 1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein kinase C. 791 39


<< Previous 1 2 3 4 5 6 Next >>